BACKGROUND:The mesenchymal stem cell secretome contains bioactive substances,cytokines,and growth factors.Three-dimensional cell culture can regulate the secretion of these components,potentially enhancing the ability to promote injury repair.OBJECTIVE:To investigate the repair effect of three-dimensional cultured human umbilical cord mesenchymal stem cell secretome on skin injuries in mice.METHODS:Human umbilical cord mesenchymal stem cells were cultured in conventional two-dimensional culture dishes and 96-well U-bottom cell culture plates,from which their secretory components were subsequently collected.The expression of skin damage repair related secretory factors in umbilical cord mesenchymal stem cells was analyzed using RT-qPCR.The protein expression level of skin damage repair related factors in umbilical cord mesenchymal stem cell secretome was detected using enzyme-linked immunosorbent assay.The potential of human umbilical cord mesenchymal stem cell secretome to repair vascular injuries was evaluated using an immortalized human umbilical vein endothelial cell migration model.A mouse skin injury model was established,and the human umbilical cord mesenchymal stem cell secretome was injected subcutaneously.Repair effects on skin injury were assessed through wound healing rates and histopathological analysis.RESULTS AND CONCLUSION:(1)After three days of cultivation,human umbilical cord mesenchymal stem cells cultured in two dimensions exhibited a fibroblast-like,swirling growth pattern,whereas three-dimensional culture led to the formation of uniform microspheres.(2)Compared with two-dimensional culture,three-dimensional culture significantly increased the mRNA expression of transforming growth factor β and basic fibroblast growth factor in human umbilical cord mesenchymal stem cells.(3)Compared with two-dimensional culture,three-dimensional cultured human umbilical cord mesenchymal stem cell secretome significantly enhanced the protein expression of vascular endothelial growth factor,interleukin-10,and granulocyte-macrophage colony-stimulating factor in the human umbilical cord mesenchymal stem cell secretome.(4)Compared with two-dimensional culture,three-dimensional cultured human umbilical cord mesenchymal stem cell secretome significantly promoted the migration of immortalized human umbilical cord mesenchymal stem cells.(5)Compared with the untreated control group and the two-dimensional cultured human umbilical cord mesenchymal stem cell secretome,the three-dimensional cultured human umbilical cord mesenchymal stem cell secretome can significantly accelerate the skin wound healing rate and wound skin structure remodeling in mice.These results indicate that three-dimensional culture can enhance the expression of paracrine factors of human umbilical cord mesenchymal stem cells,and their secretome can significantly promote the repair of mouse skin damage.

ObjectiveTo explore the application of virtual reality biofeedback training combined with oral localization therapy in dysphagia after oral cancer surgery. MethodsFrom May, 2023 to July, 2024, 86 patients with dysphagia after oral cancer surgery in Zhejiang Provincial People's Hospital were randomly divided into control group (n = 43) and experimental group (n = 43). The control group received conventional swallowing function training, while the experimental group added virtual reality biofeedback training combined with oral positioning therapy, for four weeks. The Standardized Swallowing Function Assessment Scale (SSA), Functional Oral Intake Scale (FOIS) and M.D.Anderson Dysphagia Inventory (MDADI) were used for evaluation before intervention, and two weeks, four weeks and eight weeks after intervention. ResultsFor scores of SSA , the main effects of group (F = 150.190, P < 0.001, η²_p = 0.641) and time (F = 230.870, P < 0.001, η²_p = 0.733), as well as the interaction effect (F = 16.910, P < 0.001, η²_p = 0.168) were all significant. For scores of FOIS, the main effects of group (F = 59.601, P < 0.001, η²_p = 0.415) and time (F = 89.464, P < 0.001, η²_p = 0.516), as well as the interaction effect (F = 7.990, P < 0.001, η²_p = 0.087) were all significant. For scores of MDADI, the main effects of group (F = 33.133, P < 0.001, η²_p = 0.283) and time (F = 49.650, P < 0.001, η²_p = 0.371), as well as the interaction effect (F = 3.224, P = 0.023, η²_p = 0.037) were all significant. ConclusionVirtual reality biofeedback training combined with oral localization therapy could improve the swallowing function, oral feeding ability and overall quality of life of patients with dysphagia after oral cancer surgery.

BACKGROUND:The mesenchymal stem cell secretome contains bioactive substances,cytokines,and growth factors.Three-dimensional cell culture can regulate the secretion of these components,potentially enhancing the ability to promote injury repair.OBJECTIVE:To investigate the repair effect of three-dimensional cultured human umbilical cord mesenchymal stem cell secretome on skin injuries in mice.METHODS:Human umbilical cord mesenchymal stem cells were cultured in conventional two-dimensional culture dishes and 96-well U-bottom cell culture plates,from which their secretory components were subsequently collected.The expression of skin damage repair related secretory factors in umbilical cord mesenchymal stem cells was analyzed using RT-qPCR.The protein expression level of skin damage repair related factors in umbilical cord mesenchymal stem cell secretome was detected using enzyme-linked immunosorbent assay.The potential of human umbilical cord mesenchymal stem cell secretome to repair vascular injuries was evaluated using an immortalized human umbilical vein endothelial cell migration model.A mouse skin injury model was established,and the human umbilical cord mesenchymal stem cell secretome was injected subcutaneously.Repair effects on skin injury were assessed through wound healing rates and histopathological analysis.RESULTS AND CONCLUSION:(1)After three days of cultivation,human umbilical cord mesenchymal stem cells cultured in two dimensions exhibited a fibroblast-like,swirling growth pattern,whereas three-dimensional culture led to the formation of uniform microspheres.(2)Compared with two-dimensional culture,three-dimensional culture significantly increased the mRNA expression of transforming growth factor β and basic fibroblast growth factor in human umbilical cord mesenchymal stem cells.(3)Compared with two-dimensional culture,three-dimensional cultured human umbilical cord mesenchymal stem cell secretome significantly enhanced the protein expression of vascular endothelial growth factor,interleukin-10,and granulocyte-macrophage colony-stimulating factor in the human umbilical cord mesenchymal stem cell secretome.(4)Compared with two-dimensional culture,three-dimensional cultured human umbilical cord mesenchymal stem cell secretome significantly promoted the migration of immortalized human umbilical cord mesenchymal stem cells.(5)Compared with the untreated control group and the two-dimensional cultured human umbilical cord mesenchymal stem cell secretome,the three-dimensional cultured human umbilical cord mesenchymal stem cell secretome can significantly accelerate the skin wound healing rate and wound skin structure remodeling in mice.These results indicate that three-dimensional culture can enhance the expression of paracrine factors of human umbilical cord mesenchymal stem cells,and their secretome can significantly promote the repair of mouse skin damage.

Objective:To construct and verify a risk prediction model for pulmonary infection in patients with aneurysmal subarachnoid hemorrhage (aSAH) after craniotomy and clipping, providing theoretical basis and practical guidance for improving the quality of postoperative care.Methods:Using the convenience sampling method, a retrospective selection was made of 397 patients with aSAH after craniotomy and clipping who were hospitalized in the Department of Neurosurgery of Shanxi Bethune Hospital (Shanxi Academy of Medical Sciences) from January 2019 to December 2023 as the modeling group. They were randomly divided into the training set and the test set at a ratio of 7:3, with 278 cases in the training set and 119 cases in the test set. Patients were divided into the infection group and the non-infection group based on whether they developed pulmonary infection. Univariate analysis was used to model the risk factors of pulmonary infection after aSAH craniotomy and clamping in the group, and Lasso regression was used to construct a predictive model. A total of 119 patients with aSAH admitted to the neurosurgery department of the same hospital from January to April 2024 were selected for the external validation of the model. The predictive effect of the model was evaluated through the receiver operating characteristic (ROC) curve.Results:In the modeling group, there were 216 male patients and 181 female patients. The incidence of pulmonary infection was 38.54% (153/397). Finally, five influencing factors, namely stroke, Hunt-Hess classification, mechanical ventilation, indwelling nasogastric tube and the timing of initiating enteral nutrition, were included to construct a predictive model. The areas under the ROC curves of the nomogram prediction models of this model in the training set, test set, and external validation group were 0.859(95% CI 0.791-0.928), 0.843(95% CI 0.796-0.890), and 0.800(95% CI 0.711-0.889), respectively. The calibration curve shows that the model's prediction fits well with the actual situation and has a high degree of calibration. Decision curve analysis indicates that this model has high clinical application value under different risk thresholds. Conclusions:The risk prediction model for pulmonary infection in patients after craniotomy and clipping with aSAH has good discrimination and calibration, which can provide reference for medical staff to identify high-risk patients at an early stage and take preventive intervention measures.

OBJECTIVE To analyze the pathogenic characteristics and clinical features of patients with invasive pul-monary aspergillosis(IPA)and summarize the risk factors for poor prognosis.METHODS The clinical data of 89 patients diagnosed with IPA based on microbial identification of Aspergillus from sputum or bronchoalveolar lav-age fluid cultures and diagnostic criteria,who were admitted to Zhongda Hospital Southeast University from Aug.2022 to Jul.2024 and were queried by electronic case system,were analyzed retrospectively.The distribu-tion of Aspergillus pathogens and clinical features of patients with IPA were analyzed,and the risk factors for poor prognosis were summarized.RESULTS A total of 107 Aspergillus strains were isolated from 89 cases,including 55 strains of Aspergillus fumigatus(51.40％),30 strains of Aspergillus flavus(28.04％)and 10 strains of As-pergillus niger(9.34％).There were 63 m ale patients(70.79％),and 34 cases had poor prognosis.Baseline pe-ripheral blood lymphocyte count(＜0.645×109)(OR=6.653,95％CI:2.013-21.990,P=0.002)and ICU admission(OR=8.303,95％CI:1.283-53.741,P=0.026)were identified as risk factors for poor prognosis in patients with IPA.Receiver operating characteristic curve analysis showed that the cut-off point for baseline pe-ripheral blood lymphocyte count in predicting prognosis in patients with IPA was 0.645 ×109/L,with a sensitivity of 85.22％and a specificity of 69.67％.CONCLUSIONS Baseline peripheral blood lymphocyte count and ICU ad-mission are risk factors for poor prognosis in patients with IPA.The alert value for baseline peripheral blood lym-phocyte count is 0.645 × 109/L,which has good predictive value for the occurrence of poor prognosis.

The treatment of castration-resistant prostate cancer (CRPC) faces major challenges characterized by acquired resistance to androgen deprivation therapy (ADT) and consequent aggressive tumor progression. In this context, ubiquitination and deubiquitination modifications, as key protein post-translational modifications, play a crucial role in prostate tumourigenesis and progression. In recent years, the regulation of ubiquitination and deubiquitination in CRPC by the androgen receptor signalling pathway and the tumour microenvironment has received extensive attention, and these dynamic regulatory processes have become important molecular events driving CRPC progression by affecting the proliferation, metastasis, and immune escape ability of tumour cells. Therefore, in-depth analysis of the mechanisms of ubiquitination and deubiquitination in CRPC will help develop new therapeutic targets and provide more therapeutic options for patients.

Duplicate judicial expertise has always been a difficult problem in the judicial circle.In some major,complex and difficult criminal cases,due to the objection to the appraisal conclusion,in order to ensure the impartiality and objectivity of the conclusion,the case handling organ often still needs to submit a re-appraisal.Based on the case,this paper puts forward some analysis opinions on the judicial expertise ideas of multiple cases for reference and discussion.Repeated forensic examinations have always been a challenge in the judicial system.In some major,complex,and difficult criminal cases,due to disagreements with previous assessment opinions,case-handling authorities often need to request re-evaluations to ensure the fairness and objectivity of assessment conclusions.This paper,combined with case examples,proposes several analytical perspectives on assessment approaches for cases requiring multiple evaluations,for reference and discussion among colleagues.

OBJECTIVE To analyze the clinical characteristics of the 12 patients tested with Candida auris in a three-A hospital so as to provide guidance for prevention and control of nosocomial C.auris infection.METHODS The specimens sources and departments where the C.auris strains were isolated as well as the drug resistance were retrospectively collected from Zhongda Hospital Affiliated to Southeast University between Sep.2023 and Jun.2024.The clinical characteristics of the patients with C.auris infection were summarized.The epidemiological survey was conducted for the possibility of its transmission in hospitals,and the corresponding modified preven-tion measures were put forward.RESULTS Among the 12 patients who were tested with C.auris,10 were male,and 2 were female;the age ranged between 21 and 92 years old.Most of the patients were complicated with multi-ple underlying diseases and had the history of repeated hospitalization as well as the history of invasive operation procedures such as tracheotomy,urinary catheterization,gastric tube indwelling and venoarterial catheterization;in the meantime,other multidrug-resistant organisms(MDROs)and fungi were tested in those patients,and the patients used multiple types of antibiotics.Totally 16 strains of C.auris were isolated from the 12 patients with C.auris tested,62.50％(10/16)of which were isolated from urine specimens,18.75％(3/16)were isolated from sputum specimens,and 6.25％(1/16)were isolated from deep venous catheter,tissue biopsy and wound swab specimens.All of the 16 strains of C.auris were resistant to fluconazole and sensitive to caspofungin;4 strains were resistant to amphotericin B.Totally 2 patients had Candida auris infection,one was pulmonary infection,and the other was urinary tract infection,and the infection rate was 16.67％;both patients were cured.There were 10 cases of colonization,and the colonization rate was 83.33％.The result of epidemiological survey indicated that the C.auris that was tested in the No.8 patient may originate from the No.4 patient who carelessly brought from outside the hospital due to poor implementation of standardized prevention measures.CONCLUSIONS The patients tested with C.auris usually have complicated medical backgrounds.Although the colonized C.auris strains are dominant among the strains in the hospital,the related departments need to intensify the implementation of pre-vention measures so as to prevent the transmission of C.auris and pay special attention to the early identification and management of imported pathogens.

Under the new situation of establishing the new standard system for pharmaceutical packaging materials in the 2025 edition of the Chinese Pharmacopoeia and promulgating the appendix on pharmaceutical packaging ma-terials in the Good Manufacturing Practice for Drugs,it is urgently necessary to introduce relevant standards for quality agreements on pharmaceutical packaging materials.This article focuses on analyzing the development of group standards for pharmaceutical packaging materials under the new situation,the role and significance of quality agreements for pharmaceutical packaging materials,as well as the interpretation of key parts of the"Guidelines for the Management of Quality Agreements for Pharmaceutical Packaging Materials",in order to help enterprises quick-ly shift from the original"standard-only"approach to strengthening the quality management of the entire product life cycle through quality agreements.

Duplicate judicial expertise has always been a difficult problem in the judicial circle.In some major,complex and difficult criminal cases,due to the objection to the appraisal conclusion,in order to ensure the impartiality and objectivity of the conclusion,the case handling organ often still needs to submit a re-appraisal.Based on the case,this paper puts forward some analysis opinions on the judicial expertise ideas of multiple cases for reference and discussion.Repeated forensic examinations have always been a challenge in the judicial system.In some major,complex,and difficult criminal cases,due to disagreements with previous assessment opinions,case-handling authorities often need to request re-evaluations to ensure the fairness and objectivity of assessment conclusions.This paper,combined with case examples,proposes several analytical perspectives on assessment approaches for cases requiring multiple evaluations,for reference and discussion among colleagues.